A recombinant mutant abrin A chain expressed in Escherichia coli can be used as an effective vaccine candidate.
Hum Vaccin
; 7(8): 838-44, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21817853
ABSTRACT
We used site-directed mutagenesis to mutate two key amino acid residues, Glu164 and Arg167, of abrin A chain (ABRA), creating a mutant ABRA(E164AR167L). The mutant ABRA(mABRA) encoded by mABRA(E164AR167L) was expressed in the cytoplasm of Escherichia coli, and used to develop an effective vaccine to protect mice against native abrin intoxication. The cytotoxicity of mABRA was dramatically reduced as compared to that of recombinant ABRA(rABRA) and native abrin, but the antigenicity and immunogenicity remained the same. Balb/c mice were vaccinated with purified mABRA, and survival was evaluated after challenge with native abrin. Mice that were given three vaccinations developed a protective immune response that was 100% protective against an intraperitoneal (i.p.) administration of 10×LD50 of native abrin. Furthermore, the sera from immunized mice provided complete passive protection for naive mice. This study describes the generation of a substantial amount of mABRA from E. coli and the potential application of mABRA as an effective vaccine candidate for humans, to protect against a high-dose of native abrin.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes
/
Vacinas Sintéticas
/
Abrina
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article